Olodaterol hydrochloride is a beta-selective adrenoceptor agonist with potent bronchodilator activity. Olodaterol is chemically known as 6-hydroxy-8-[(1R)1-hydroxy-2-[2-(4-methoxy-phenyl)-1,1-dimethyl-ethylamino]-ethyl]-4H-benzo[1,4]oxazin-3-one. A particularly preferred pharmaceutically acceptable salt of olodaterol is olodaterol hydrochloride monohydrate.
The process for preparing Olodaterol is described in patents U.S. Pat. No. 4,460,581, US 2010022770 and US 2011124859. One of the key steps in the process is reacting an epoxide, such as 8-(2R)-oxiranyl-6-substitued oxy-4H-benzo[1,4]oxazin-3-one [Formula (I)] with an amine, such as 2-methyl-1-(4-methoxy-phenyl)-2-propanamine [Formula (II)] to form an intermediate 6-substituted oxy-8-[(1R)-1-hydroxy-2-[[2-(4-methoxy-phenyl)-1,1-dimethyl-ethyl]-amino]-ethyl]-4H-benzo[1,4]oxazin-3-one [Formula (IIIa)].

The drawback of this process is that the opening of epoxide ring is not regioselective and thereby resulting in formation of substantial quantities of impurities as by products, Formula (IIIb) and Formula (IIIc), resulting in overall lower yields. The quantity of 2-methyl-1-(4-methoxy-phenyl)-2-propanamine used in this step is also large excess than theoretical amounts.
Accordingly, there is a need for developing a more efficient process for preparing Olodaterol salts especially for large scale production with higher yields.